Update in Urinary and Male Genital Tracts Pathology

13th - 17th of April 2016

Spindle Cell Lesions ad Tumors

Antonio Lopez-Beltran
Lisbon, PT
67 y man with history of hematuria
Cystoscopic examination revealed
A polypoid mass
 Main Differential Diagnosis
• Sarcomatoid carcinoma
• Inflammatory myofibroblastic tumor
– Postoperative spindle cell nodule
• Leiomyosarcoma
• Others
• Urothelial carcinoma with pseudosarcomatous
stromal reaction
– Rhabdomyosarcoma
– Angiosarcoma
– Sarcoma NOS/Malignant fibrous histiocytoma
• Histology+IHC+Clinical information
Sarcomatoid Carcinoma

CK AE1/3
CD10
SARCOMATOID CARCINOMA

p63

CK 5/6 or HMCK p63

 Sarcomatoid Carcinoma
• “Sarcomatoid carcinoma” should be used for all biphasic
malignant spindle cell neoplasms exhibiting morphologic and or
IHC evidence of epithelial and mesenchymal differentiation
(with presence or absence of heterologous elements
acknowledged in the diagnosis).
• Mean 66 y, male, previous X-Ray or cyclophosphamide .
• Heterologous: OS, and ChS
• Micro: Uca, adenoca, scc
– Myxoid form
• 70% died in 1-48 months
• Genetics: clonal origen of both components
• DD: myofibroblastic lesions
Sarcomatoid Carcinoma

Lopez-Beltran et al 1998
Sarcomatoid Carcinoma with
Heterologous Component
Chondrosarcoma
S100
 Sarcomatoid Carcinoma with
Heterologous Component
Liposarcoma Leiomyosarcoma
Cheng/Lopez-Beltran Bladder Pathology, Wiley, 2012
 IHC-Spindle cell lesions UB

Antibody IMT Sarcomatoid Leiomyosarcoma Rhabdomyosarco

Carcinoma ma
         

ALK1 20-89% 0% 0-10% 20%

Muscle associated markers
SMA 63-100% 15-80% 43-100% 97%
Desmin 27-80% 0-40% 0-60% [35-75%] 97 -100%
h-caldesmon 0-67% N/A 100% [18-57%] 0%
Calponin 89% N/A 100% [57-90%] 0%
MyoD1 0% 0%** N/A [0%] 100%

Myogenin 0% 0%** 0% 76-100%

Epithelial associated markers
Pan 36-89% 67-100% 0-58% N/A [6% (focal)]
cytokeratin
(AE1/AE3)
EMA/MUC1 0-50% 50-100% 0-12% N/A [6% (focal)]
P63 0% 50-58% 23% N/A [5% weak or
focal]
HMCK(34βE12) 0% 0-27% 0% N/A
CK5/6 0% 27-65% 0% N/A
OSCAR 70% 68% 54% N/A
Amin, Trpkov, Lopez-Beltran, et al.
Sarcomatoid Carcinoma, Myxoid Variant
Inflammatory Myofibroblastic Tumor (Lott, 2007)
Male 13 years of age with
hematuria
Macroscopical findings:
polypoid mass >> left lateral
bladder wall
Rare Associated
necrosis!
Male
65 y
 Inflammatory Pseudotumor (Inflammatory
Myofibroblastic Tumor)
• Polypoid or pedunculated lsions that mimic sarcoma/sarcomatoid carcinoma
• Infiltrative growth
• Clonal proliferation of myofibroblasts
• ALK+ by IHC and and gene translocation by FISH (60%)
• Immunohistochemical findings: Focal positive cells for cytokeratin, actin, and vimentin.

Entity Typical Immunoprofile

IMT AE1/AE3+, (p63, HMCK, CK5/6 )-, SMA+, desmin+/-,

ALK1+/-
LMS (SMA, desmin)+, (p63, HMCK, CK5/6 )-/+, AE1/AE3-, ALK1-

Sarcomatoid Uca AE1/AE3+, (p63, HMCK, CK5/6) +/-, SMA -/+, desmin -,
ALK1-
RMS desmin+, keratin- , (p63, HMCK, CK5/6)-, SMA+, ALK1-/+
 Cheng et al J Urol 280: 1235, 2008

FISH detection of ALK (anaplastic lymphoma

kinase) translocation may be useful for predicting
recurrence of IMT.
Inflammatory Pseudotumor (Inflammatory
Myofibroblastic Tumor)

• DD
• Urothelial carcinoma with sarcomatous stroma
• Leyomiosarcoma
• Postoperative Spindle Cell Nodule
 Urothelial Carcinoma with
Pseudosarcomatous Stromal Reaction
 Postoperative Spindle Cell Nodule
• After surgical procedure
• Plump elongated spindle
cells
• Infiltrate the bladder wall
• Quite cellular
• Mitosis present but not
atypical
• Myofibroblasts
 Mesenchymal Tumors of the Urinary
Bladder
• Leiomyoma is the most
frequent • Rhabdomyosarcoma
– Children, 4 years
– Other sites – Polypoid w/wout botryoid
• Leiomyosarcoma – Cambium layer
– Rare in adults
– Adults
• Other:
– Variable size
• angioma vs. angiosarcoma
– Other sites • fibroma, neurofibroma;
– Same criterias as uterine solitary fibrous tumor; MFH;
cases PNET
– May be myxoid • DD Sarcomatoid carcinoma
and others
 Leiomyosarcoma
• Most common malignant mesenchymal tumor
of the urinary bladder in adults
• <1% Bladder tumors
• 6th-8th decade; 15-75 y; Male 2:1
• Some after cyclophosphamide
• Gross hematuria 80%
• >60% of patients developing metastases or
dying of recurrent or metastatic tumor
• Higher-grade tumors had a worse prognosis.
Most low grade tumors have lower risk of
recurrence or metastasis
• Radical Surgery
• Often Large and polypoid
 Leiomyosarcoma
• Low-grade leiomyosarcoma should be
made for a cellular tumor with some
mitotic activity
• (<5 mitotic figures per 10 hpf), mild to
moderate cytologic atypia, minimal
necrosis, and an infiltrative margin)
• High-grade leiomyosarcoma as having
moderate to marked cytologic atypia
• with more than 5 mitotic figures per 10
hpf and/or abundant necrosis.
Entity Typical Immunoprofile

IMT AE1/AE3+, (p63, HMCK, CK5/6 )-, SMA+, desmin+/-,

ALK1+/-

LMS (SMA, desmin)+, (p63, HMCK, CK5/6 )-/+, AE1/AE3-, ALK1-

Sarcomatoid Uca AE1/AE3+, (p63, HMCK, CK5/6) +/-, SMA -/+, desmin -,
ALK1-

RMS desmin+, keratin- , (p63, HMCK, CK5/6)-, SMA+, ALK1-/+

Amin, Trpkov, Lopez-Beltran et al

Baumgart et al. Clin Cancer Res 2007;13:1685
Sarcomatoid Carcinoma of the Bladder
A Model of Epithelial-Mesenchymal Transition

The histogenesis of the

tumor, particularly the
co-existence of
epithelial and
sarcomatous
components, has not
been elucidated
Concordant p53 Mutation in Sarcomatoid Carcinoma

Sung et al. J Pathol 211: 420, 2007

Loss of Heterozygosity (LOH)
As Clonal Marker

N T
 LOH and X-Chromosome Inactivation Analysis

N: Normal
TCC: Transitional cell
carcinoma
SC: Sarcomatoid Ca

Sung et al J Pathol
211: 420, 2007
Cheng et al Am J Surg Pathol 35:e34, 2011
 Conclusion

• Histology
• IHC
•Clinical History

Sarcomatoid Ca Leiomyosarcoma IMT

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